Jacqueline Palfy (Host): Hi, I’m Jacqueline Palfy with Sanford Health News and I’m here today with Dr. Steven Powell, an oncologist. How are you doing today?
Steven Powell, MD (Guest): I’m doing well, how are you?
Host: I’m doing okay. So, we have been doing a series of podcasts where we have been talking to a bunch of our folks about personalized medicine and a lot about cancer lately. Talk to me a little bit about what personalized medicine in cancer is.
Dr. Powell: Yeah, I mean I think it’s actually a term that has had a lot of buzz around it lately but for a long time, we’ve been doing personalized medicine in cancer.
We oftentimes personalize chemotherapy to a specific patient or their cancer type but now kind of the modern era of medicine when we think of personalized medicine, or precision oncology, what we’re thinking is actually looking at the tumor itself, finding out what’s causing that tumor to grow or to avoid being destroyed and trying to use treatments that will actually specifically target that specific cancer in that patient.
So, it may be unique to that patient or unique to that cancer type.
Host: You know I think you’re right. It is definitely a buzz word and doctors have been tailoring treatments to their patients since the first doctor treated the first patient, right? But now you just have so much more information.
Dr. Powell: Absolutely. I think we’re kind of at the forefront of our treatments really coming into play right now.
I think we’ve learned a lot about cancer over the past 100 years. I mean 100 years ago, we really didn’t know what caused cancer or what made cancer cells and over this time, we’ve just had a dramatic improvement in knowing the genetics of cancer, knowing how the immune system interplays with cancer and knowing how other factors about your diet and the environment around you can have an impact.
So, I think now all that information is at our fingertips and we can utilize that information to try to tailor treatments to best treat the cancer.
Host: When you first became interested in medicine, did you come into it because you wanted to do research, because you wanted to be a doctor or because you were just way into cancer?
Dr. Powell: It was probably a combination of all three of those things. I worked in a cancer research lab as an undergraduate. I was an engineering major.
Host: OK, I hear a lot of doctors that say they used to be some kind of engineering major or something. How does that translate?
Dr. Powell: I mean we like to solve problems, I guess. And I guess that fits into the research part of it. As an engineer, a lot of your training is trying to figure out here’s your problem, what’s the best way to attack this? And you really come at it from all kinds of different angles to try to come up with the best solution.
And from a research perspective, trying to find new drugs, that was very interesting to me is learning the biology of cancer and how it works. How do you intervene and manipulate and treat the most effective way possible?
Host: How has that changed since you first started practicing?
Dr. Powell: I mean I think cancer treatment has changed dramatically in many good ways since I started. I mean when I was in Fellowship, I still remember our treatments for melanoma, we had a chemotherapy drug for instance and that was it and people lived on average seven months with stage 4 melanoma and by the end of my training in 2013, it completely changed.
We don’t even hardly use chemotherapy anymore for melanoma. Now we are using things like immunotherapy and targeted therapies because we know so much more about how the cancer grows and how we can try to use treatments against it.
Host: How does that feel as a physician to sort of be on the front of a freight train, watching all of these changes happen?
Dr. Powell: I think it’s great because and we are seeing more and more people wanting to go into oncology and to be oncologists because traditionally it was an area where we didn’t have a lot of treatments and chemotherapy does work. It certainly does work for certain cancers, but it doesn’t work for all cancers. And when we talk about incurable cancers it only can work for so long.
So, to be able to have all these options available now and you can tailor them to each specific patient, I think it’s really rewarding. And it allows you to really try to tailor your treatments so people can live longer, feel better and in many cases now, we are actually seeing cancers that were not curable, potentially curable.
Host: So, becoming an oncologist may be a more hopeful career now than it used to be?
Dr. Powell: Absolutely. I know it’s changed quite a bit.
Host: That must feel good. I would think that feels really good to sit across the table from someone and give them better news than you could have when you started.
Dr. Powell: Oh absolutely. I think now anybody hears the word cancer and immediately you stop listening at that point. It’s cancer. It’s a horrible diagnosis. But I think the important thing now or what we can actually tell people is well you do have cancer, but we have these treatment options that are good treatment options and maybe now we have a cure for this when we previously didn’t.
Host: Well one of the ways that we are able to find some of these cures or see if something will or won’t work is through clinical trials. We’ve talked before that at Sanford Health, we have over 300 clinical trials at any given time which seems astonishing. And you have had a fair amount of success in some of these. Can you tell me a little bit about that?
Dr. Powell: Yeah, I mean I think clinical trials are very important. They are oftentimes someone’s first chance at getting a new treatment and I think that that’s why one of the main reasons I went into oncology is I worked in a lab.
I developed these treatments but if you never get to use them, you never get to give patients access to them; they will never make it as an option. And I think so one of my goals is to try to bring in these exciting treatments and we’ve brought in a number of clinical trials in cancer and probably our most successful trials have been with a drug called pembrolizumab or Keytruda is the trade name for that drug.
Host: I don’t know which ones of those names is harder to say. I know which one’s harder to spell. So, tell me a little bit about that trial which you recently spoke about.
Dr. Powell: Yeah. So, our first study of Keytruda in lung cancer was actually a study called Keynote-21 and we opened that I believe it would have been in 2015 here so we are one of only a few sites in the country that had it. And it was actually — that study was — they didn’t even have a name for Keytruda then. It was called MK3475, so this was like brand new before we even knew it did anything. We knew that it had some success in lung cancer, but it started out as a what we call an early phase clinical trial.
So, part of that study we asked the question what happens if you take our standard chemotherapy for lung cancer and you add Keytruda to it? Can it augment the effect of chemotherapy? And the findings from that initially were very profound and it essentially doubled the response to treatments. So, patients having their cancers shrink — they had twice as much chance of having their cancer shrink by adding Keytruda to the chemotherapy.
Host: That’s crazy.
Dr. Powell: I mean it was a big deal at the time and it also dramatically improved how long patients could live with stage 4 lung cancer at the time. So, it was kind of a big deal at the time. It was a big first step in lung cancer so to say.
Host: What’s the prognosis in general for lung cancer for the folks listening at home?
Dr. Powell: Yeah, I mean on average, for somebody with stage 4 lung cancer — just as a whole, back when this study started — it was about a year. That was the average survival and what these studies have shown that it actually has extended that maybe even up to two years or longer depending on how patients do with treatment.
Host: What’s your major risk factor for getting lung cancer? Is it still smoking?
Dr. Powell: Still smoking is our number one risk factor. That’s probably the predominant reason for it. and then there’s some unknowns. We don’t even know what the vaping and e-cigarettes and all that, what it’s going to do but I think smoking right now is probably the biggest.
Host: So, and there’s still a huge population at risk then. So, an enormous amount of people who could be helped from this study. I think it’s always important every time we talk about clinical trials to remind our folks that when you go on to agree to be part of a clinical trial, you still get the standard of care, you just get something else too.
Dr. Powell: Absolutely. I mean so Keynote-21 which was our first study that did this, patients actually knew exactly what they were getting and the question was, was doing the combination with chemotherapy better or not? And patients knew when they went on it and then actually the patients that — this is often something in clinical trials, if you don’t get the new treatment initially, they are offered the new treatment if their initial treatment stopped working. So, all patients actually got access to the immunotherapy on the trial.
Host: Which is amazing to be able to — especially because it showed such improvement to have access to that here. So, then what happened after that trial?
Dr. Powell: So, after that trial, that lead to Keynote-189 which is the other study that was a big clinical trial. So, that was a massive study. So, anytime — so when you do a clinical trial, the first step is to see does the drug look like it’s beneficial. And then the next trial say is this better than doing what we are doing now and at the time, what we were doing now worldwide was chemo for lung cancer. And like I said the average estimated survival would be about a year. So, that was the big effort to compare these head to head.
So, chemo versus chemo plus immunotherapy is what Keynote-189 was. And it was an international trial of multiple sites. Our site, Sanford, was one of the U.S. sites involved with it but I mean this was in numerous countries. I can’t remember the exact number, but I want to say it was in over 30 countries they had this.
Host: Wow. Tell me — describe what immunotherapy is.
Dr. Powell: Yeah, I mean immunotherapy, it encompasses a lot of different treatments but the general idea of immunotherapy in cancer is drugs that actually activate or use your own immune system to fight or attack the cancer.
Host: OK. So, you recently presented on this at a conference in Spain and what is the update on this?
Dr. Powell: Yeah so —
Host: Which was pretty exciting to be at.
Dr. Powell: To be able to go to an international conference, being from Sioux Falls, South Dakota, is kind of a big deal. But so the major finding of this is actually we wanted to look specifically at patients that had brain metastases.
So, with lung cancer, about a third of patients unfortunately the cancer spreads to their brain. And in that situation, actually the average survival typically is only about nine months. So, it’s a pretty bad prognosis.
So, what we actually did is we looked at Keynote-21, Keynote-189 which we were part of and then also a third study, Keynote-407, which looked at a separate type of lung cancer. And we looked to see how did people do that had the brain metastases where it had spread to the brain versus the people that didn’t? And we wanted to compare how they did.
And what that study — what this analysis showed is that when we initially what I told you nine months is the expected survival of somebody with brain metastases with just chemo — this actually extended the average survival to 18 months. Yeah, it doubles it and actually in this study, when they looked at the people in the studies, their survival was only seven and a half months for the people that got chemo alone. So, it actually almost nearly tripled it.
So, I mean it was a big deal to do that because when cancer spreads to the brain, it’s very difficult to treat. Chemotherapy doesn’t go there. Small amounts will. But it’s not very effective in the brain. Our only treatments are usually radiation. So really the idea behind this is that perhaps these immunotherapies are actually allowing the immune system to get into the brain and help control the cancer.
Host: It seems short of miraculous.
Dr. Powell: It is. I mean I personally have had two people that had this exact treatment that have been going over two years now without their cancer coming back or growing in the brain and they showed up with spots on the brain where normally it would be unheard of for somebody to live that long when the cancer had spread to the brain.
Host: So, what is next for this?
Dr. Powell: Yeah, I mean so we’re going in a lot of different directions. I think the immunotherapies like Keytruda and Opdivo and some of these others that you are hearing about right now; they are here. We are using them in our treatments, but we are actually now using them to try to cure cancers earlier on.
So, when we catch cancer early, how do you use these treatments to try to improve our cure rates? Maybe with surgery or maybe with radiation or maybe even with chemotherapy. So, I think that area is moving pretty rapidly, and we have a number of clinical trials doing that in a number of different cancers.
My interest is how do we build on immunotherapies? How do we use newer immunotherapies? So, we have a lot of newer early phase clinical trials as I said before, Keytruda started out as a basically a code name. So, we have those new treatments that are now in early phase clinical trials ranging all the way from viruses that actually can destroy cancers and spread and activate the immune system. We have a couple trials going on right now with that.
We have some other really interesting immunotherapies that actually inject directly into the tumor and it stimulates an immune response to that cancer. And then we even now have vaccines that can train your immune system to try to attack cancer specifically.
So, that’s kind of our next wave of attack is bringing in these more novel or newer treatments that are trying to come after the cancer from a different angle so to say. Because ultimately, what’s going to be what we need is we are going to have to combine these together in the right way specifically for a patient?
So, that’s to me, where precision oncology or precision medicine is going is we’re going to try to figure out what specific makeup is going on in the cancer at that point in time and how do you use these therapies wisely together to try to modulate the immune response or even maybe even use things like chemotherapy or targeted therapies to get rid of the cancer.
Host: So, just like now, when we’re doing the first sort of — not the first but some of these trials where it’s chemotherapy plus Keytruda, someday it will be this plus this plus this. We just keep adding to see as we learn more?
Dr. Powell: Yeah, I mean I think it’s going to be much more of an orchestra, right. Not adding everything together but first we’re going to have this section play and then this section is going to play and then everybody is going to play together. I mean, that’s where it’s going. I think the traditional approach when we were developing chemo is was like well this worked. Let’s add another one and let’s add. And we find side effects, that becomes an issue. But I think we’re going to really orchestrate these treatments together in a fashion so that they will work as effective as possible.
Host: I think that’s amazing. And thank you so much for coming on today and talking to me about this. And we’ll definitely have you on again to see what happens next.
Dr. Powell: All right. Thank you.